Biomedical subjects

R E J Dyball

Publications and source records attributed to R E J Dyball.

8 recordsLinked to original sources

PubMed2006

Pinealectomy reduces optic nerve but not intergeniculate leaflet input to the suprachiasmatic nucleus at night.

The suprachiasmatic nucleus (SCN) of the hypothalamus regulates circadian rhythms in mammals. It receives, among others, direct inputs from the retina and from the thalamic intergeniculate leaflet (IGL). The former sends photic signals to the SCN, whereas the latter probably integrates photic and nonphotic information. To characterise these inputs in vivo, extracellular single-unit recordings were made from the SCN of rats under urethane anaesthesia during electrical stimulation of the optic nerve (OptN) or the IGL region. Cell responses were evaluated by creating peri-stimulus time histograms. Because humoral signals such as melatonin might modulate the activity of the SCN in addition to neural inputs, recordings were also made using pinealectomised (Px) rats to test for a possible role of this hormone in regulating inputs to the SCN. A significantly greater number of cells responded to IGL (60 of 90, 67%) than to OptN (35 of 75, 47%) stimulation in intact animals (chi(2) = 5.905, P = 0.015). The same was true when Px animals were tested (IGL, 82 of 131, 63%; OptN, 31 of 111, 28%; chi(2) = 27.637, P < 0.001). In intact animals, the proportion of cells responsive to IGL stimulation during the day and during the night was not significantly different from the proportion responsive in Px animals. The same was true for OptN stimulation during the day. However, during the night, the proportion of cells responsive to OptN stimulation in intact animals was significantly greater than the proportion responsive in Px animals (chi(2) = 7.127, P = 0.008). Our findings suggest that a lack of melatonin modulates OptN but not IGL inputs to the SCN.

Animals↗

PubMed2005

Spike coding during osmotic stimulation of the rat supraoptic nucleus.

Novel measures of coding based on interspike intervals were used to characterize the responses of supraoptic cells to osmotic stimulation. Infusion of hypertonic NaCl in vivo increased the firing rate of continuous (putative oxytocin) cells (Wilcoxon z= 3.84, P= 0.001) and phasic (putative vasopressin) cells (z= 2.14, P= 0.032). The irregularity of activity, quantified by the log interval entropy, was decreased for continuous (Student's t= 3.06, P= 0.003) but not phasic cells (t= 1.34, P= 0.181). For continuous cells, the increase in frequency and decrease in entropy was significantly greater (t= 2.61, P= 0.036 and t= 3.06, P= 0.007, respectively) than for phasic cells. Spike patterning, quantified using the mutual information between intervals, was decreased for phasic (z=-2.64, P= 0.008) but not continuous cells (z=-1.14, P= 0.256). Although continuous cells showed similar osmotic responses to mannitol infusion, phasic cells showed differences: spike frequency decreased (z=-3.70, P < 0.001) and entropy increased (t=-3.41, P < 0.001). Considering both cell types together, osmotic stimulation in vitro using 40 mm NaCl had little effect on firing rate (z=-0.319, P= 0.750), but increased both entropy (t= 2.75, P= 0.010) and mutual information (z=-2.73, P= 0.006) in contrast to the decreases (t= 2.92, P= 0.004 and z=-2.40, P= 0.017) seen in vivo. Responses to less severe osmotic stimulation with NaCl or mannitol were not significant. Potassium-induced depolarization in vitro increased firing rate (r= 0.195, P= 0.034), but the correlation with decreased entropy was not significant (r=-0.097, P= 0.412). Intracellular recordings showed a small depolarization and decrease in input resistance during osmotic stimulation with NaCl or mannitol, and membrane depolarization following addition of potassium. Differences in responses of oxytocin and vasopressin cells in vivo, suggest differences in the balance between the synaptic and membrane properties involved in coding their osmotic responses. The osmotic responses in vivo constrasted with those seen in vitro, which suggests that, in vivo, they depend on extrinsic circuitry. Differences in responses to osmolality and direct depolarization in vitro indicate that the mechanism of osmoresponsiveness within a physiological range is unlikely to be fully explained by depolarization.

Action Potentials↗

PubMed2004

Rhythmic changes in spike coding in the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus is regarded as the main mammalian circadian pacemaker but evidence for rhythmic firing of single units in vivo has been obtained only recently. The present study was undertaken to determine if rhythms could be seen using measures of activity in addition to the mean spike frequency. We investigated whether there were changes in the irregularity of cell activity measured by the disorder of the interspike interval distribution for neurones recorded in vivo and in vitro. By plotting the entropy of the log interval histogram that quantifies the coding capacity for each action potential against the respective zeitgeber time, we describe oscillations of spike activity in vivo. Entropy measures have the advantage over variances in that they quantify aspects of the shape of the distribution and not just the dispersion. One hundred and sixty-six cell recordings from the suprachiasmatic nucleus showed a significant rhythm in entropy with an oscillatory trend in the data (P < 0.001) showing a trough towards the end of the light period and a peak in the mid-dark period. There was a similar rhythm for the cells recorded from the peripheral zone (n = 209, P = 0.037). In separate experiments in vitro, to investigate the relationship between mean spike frequency and entropy, potassium-induced depolarization of cells recorded during the subjective night was correlated with a significant increase in mean spike frequency (r = 0.259, P = 0.011) and a decrease in entropy (r = -0.296, P = 0.004). The negative correlation between the entropy and mean spike frequency of cells recorded in vitro was significantly different from that seen in vivo (F = 15.5, P < 0.001), which may reflect differences in the balance between deterministic and stochastic influences on spike occurrence. The study shows that while there is a rhythm of mean spike frequency, parameters based on the variability of interspike interval distributions also display rhythmic changes over the day-night cycle.

Action Potentials↗

PubMed2004

Responses of cells in the rat supraoptic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle.

To determine whether the daily rhythms of spike activity in the supraoptic nucleus (SON) were accompanied by changes in the behaviour of its inputs, we used conventional extracellular single cell recordings from cells in the SON of anaesthetized rats while stimulating the contralateral optic nerve and the ipsilateral suprachiasmatic nucleus (SCN). Neurones in the SON region were identified by antidromic activation and classified as oxytocin or vasopressin cells, on the basis of their spontaneous firing patterns. Approximately 27% of both oxytocin (29/108) and vasopressin (39/147) neurones were excited by stimulation of the optic nerve, and the majority of responses had a long latency (>20 ms). Very few oxytocin (3/108) and vasopressin cells (2/147) were inhibited by stimulation of the optic nerve. The pattern of the responses (excitatory, inhibitory or nonresponsive) of oxytocin and vasopressin cells to stimulation of the optic nerve was significantly related to the time of day (chi-square test; P = 0.012, oxytocin cells; P = 0.006, vasopressin cells). The proportion of oxytocin cells excited by stimulation of the optic nerve was highest at ZT 4-8 and lowest at ZT 20-24. For vasopressin cells, it was highest at ZT 12-16 and lowest at ZT 20-24. The proportion of excitatory, inhibitory and complex responses seen in oxytocin and vasopressin cells following stimulation of the SCN also changed and was significantly different at different times of day (oxytocin cells: highest proportion of excitatory responses at ZT 12-16, P = 0.029; chi-square test; vasopressin cells: highest proportion of excitatory responses at ZT 0-4, P = 0.005; chi-square test). Thus, inputs to oxytocin and vasopressin neurones from the optic nerve and some outputs from the SCN changed during the light/dark cycle. Such changes may contribute to the generation of 24-h rhythms in activity of oxytocin and vasopressin neurones and release of the peptides.

Animals↗

PubMed2004

Assessment of spike activity in the supraoptic nucleus.

Novel approaches to the characterization of coding carried by spike trains are discussed. Measuring firing frequency alone may only partially reflect spike patterning, and can only quantify changes of the most obvious kind. We have devised a method that combines probabilistic and information approaches to quantify the variability of the interspike intervals in a way that is independent of spike frequency. To illustrate the technique, the firing of an oxytocin cell and a vasopressin cell were compared before and after osmotic stimulation. A bimodal lognormal function was fitted to the interspike interval histograms. The entropy of the log interval histogram was used to measure the variability of intervals and to reflect the coding capacity of the cell per spike. A perfect metronome shows no variability in interval and thus has no greater coding capacity than is conveyed by its frequency, whereas the variability of intervals of magnocellular neurones means that their irregular activity has greater potential for coding. While the mean spike frequency increased in both the oxytocin and vasopressin cells in response to osmotic stimulation, the changes in their irregularity showed differences. Osmotic stimulation reduced the entropy of the oxytocin cell, reflecting an increase in the regularity of its spike activity. Conversely, osmotic stimulation had little effect on the entropy of the vasopressin cell. Such differences are not evident from a simple inspection of ratemeter activity. The comparison highlights the limitations of mean spike frequency as a measure of spike coding. Parameters based on the interspike intervals constitute informative measures of spike activity that allow objective comparisons to be made between the activity under different physiological conditions.

Action Potentials↗

PubMed2003

Measuring spike coding in the rat supraoptic nucleus.

Measuring spike coding objectively is essential to establish whether activity recorded under one set of conditions is truly different from that recorded under another set of conditions. However, there is no generally accepted method for making such comparisons. Measuring firing frequency alone only partially reflects spike patterning. In this paper, novel quantities based on the logarithmic interspike intervals are proposed as useful measures of spontaneous activity. We illustrate the methods by comparing extracellular recordings from magnocellular cells of the rat supraoptic nucleus in vivo and in vitro and between oxytocin and vasopressin cells in vivo. A bimodal Gaussian function fitted to the log interspike interval histogram accurately described the distribution profile for very different types of activity. We introduce the entropy of the log interval distribution as a novel quantity that measures the capacity of a cell to encode information other than a constant instantaneous frequency. Unlike existing entropy measures that are based on spike counts, it quantifies the variability in the interval distribution. In addition, the mutual information between adjacent log intervals is proposed as an objective measure of patterned activity. For cells recorded in vivo and in vitro, there was no significant difference in mean spike frequencies but there were differences in the log interval entropy (t = -4.97, P < 0.001) and the mutual information (z = -2.64, P < 0.01). The differences may result from the disruption of connections in the slice preparation. When a comparison was made between the spike activity of oxytocin and vasopressin cells recorded in vivo, there was a difference in mutual information (z = 5.15, P < 0.001) but not in mean spike frequency. Both comparisons highlight the potential limitations of using mean spike frequency alone as a measure of spike coding. We propose that our novel parameters based on interval analysis constitute informative measures of spontaneous activity under different physiological conditions.

Action Potentials↗

PubMed2003

Responses of cells in the rat suprachiasmatic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle.

Conventional extracellular recordings were made from single cells in the suprachiasmatic nucleus (SCN) region of the anaesthetized rat. Each cell was tested for its response to stimulation at three sites; the contralateral optic nerve, the ipsilateral supraoptic nucleus (SON) or the ipsilateral arcuate nucleus (ARC) to determine whether the behaviour of the synapses in the SCN was different at different times. Responses to stimulation were tested once each hour and assessed by creating peristimulus time histograms. Excitatory, inhibitory or complex (consisting of more than one component) responses were seen. The responses of some cells that were recorded for several hours changed with time. Changes were seen in the responses of SCN cells to stimulation of the ARC (31/91 cells) and the SON (26/90 cells) regions, but only rarely to stimulation of the optic nerve (2/72 cells). Such differences in proportion are unlikely to have occurred by chance (P < 0.001; chi-square test). Changes seen included the appearance of both excitatory and inhibitory responses in cells that were initially unresponsive. In some cells, one component of a complex response remained constant while another component changed with time. When the cells in the SCN were treated as a group, the proportion of excitatory, inhibitory or complex responses to ARC stimulation did not remain constant throughout the light/dark cycle (P = 0.014; chi-square test). The proportion of excitatory, inhibitory or complex responses to SON and optic nerve stimulation showed no significant variation with the light/dark cycle. If a change in response can be interpreted as a change in the behaviour of a neural connection, the results imply that some of the projections to the SCN from within the hypothalamus change at different times of the light/dark cycle, whereas no change could be seen in the input from the optic nerve. Thus, some of the connections of the SCN appear not to be hard wired, but change rapidly with time.

Afferent Pathways↗

PubMed2003

Defined cell groups in the rat suprachiasmatic nucleus have different day/night rhythms of single-unit activity in vivo.

The electrical activity of the rat suprachiasmatic nucleus (SCN) was examined in anesthetized rats in vivo using single-unit electrophysiological techniques. The present data confirm the daily variation in the electrical activity of the SCN previously reported in vitro and in vivo using multiple-unit recording techniques. They further suggest that subpopulations of suprachiasmatic neurons with different neural connections have a different daily rhythm of activity. Neurons in the SCN region showed a significant rhythm of activity (p = 0.034; Kruskall-Wallis analysis of variance [KW-ANOVA]). The greatest activity occurred during the second part of the light period (ZT 10-12), and the lowest activity occurred in the early part of the light period (ZT 0-2). The subgroup of cells in the suprachiasmatic region with output projections to the arcuate nucleus (ARC) and/or supraoptic nucleus (SON) regions also showed a significant rhythm (p = 0.001; K-W ANOVA). Their activity appeared to show two peaks near the light-dark (ZT 10-12) and dark-light (ZT 22-24) transition periods with the lowest activity at ZT 16-18. This rhythm was significantly different (p = 0.016) from that of neurons without an output projection to the ARC and/or SON. Retinorecipient suprachiasmatic neurons appeared to have a less robust daily rhythm in their activity. The change in the firing behavior of the cells was not reflected simply by changes in mean firing rate. Examination of the coefficient of variation of the interspike interval distribution of cells at different times of day revealed changes in the firing pattern of cells in the SCN region that did not have output projections (p = 0.032; K-W ANOVA). The present results thus suggest that the SCN is composed of a heterogeneous population of neurons and that different rhythms of activity are expressed by neurons with different neural connections. There were changes in both firing pattern and firing rate.

Animals↗